不同浓度芬太尼对大鼠脑片缺氧缺糖损伤的保护作用  

Protective effects of high concentration fentanyl on brain slice injury induced by oxygen glucose deprivation

作　　者：郑拥军[1] 王祥瑞[1] 吴兴军[2] 陈红专[2] 赵延华[1] 苏殿三[1] 潘志英[1] 

机构地区：[1]上海第二医科大学附属仁济医院麻醉科,上海200001 [2]上海第二医科大学药理学教研室,上海200001

出　　处：《中国药理学通报》2005年第10期1246-1250,共5页Chinese Pharmacological Bulletin

摘　　要：目的探讨高浓度芬太尼对大鼠脑片缺氧缺糖损伤的保护作用及其机制。方法建立大鼠脑片缺氧缺糖损伤模型,设立对照组(Control)、缺氧缺糖损伤组(OGD)、芬太尼50μg.L-1组(F50)、芬太尼500μg.L-1组(F500)。利用2,3,5-三苯基氯化四氮唑(TTC)染色定量比色、乳酸脱氢酶(LDH)、免疫组化、电镜评价高浓度芬太尼对脑损伤的保护作用。同时激光共聚焦显微镜测定脑片胞内钙变化。结果不同浓度芬太尼(50、500μg.L-1)抑制脑片OGD损伤所致的TTC染色降低;减少LDH释放;减轻神经元凋亡,改善神经元超微结构的病理损伤。OGD损伤增加bax和bc l-2蛋白表达,增加胞内钙离子浓度。不同浓度芬太尼(50、500μg.L-1)进一步上调bc l-2蛋白表达,降低bax蛋白表达,同时抑制胞内钙离子浓度。与芬太尼500μg.L-1相比,芬太尼50μg.L-1作用较强。结论高浓度芬太尼具有脑保护作用,能够抑制缺氧缺糖损伤导致的大鼠脑片神经元损伤及其凋亡过程,且芬太尼对于胞内钙离子的调控可能是其发挥保护作用的重要机制之一。随着芬太尼的剂量增加,其保护作用减弱,但在临床应用的剂量范围内未见明显的毒性作用。Aim To investigate the protective effects of high concentration fentanyl on the brain slice injury induced by oxygen glucose deprivation （OGD）. Methods Rat brain slices were made and randomly assigned to four groups ： control （ n =10 ） , OGD （ n =10 ） , fentanyl 50μg· L^-1 （ F50, n = 10 ） and fentanyl 500 μg· L^-1（F500, n = 10）. Changes of the neuron injury and apoptosis were observed with TTC staining, LDH releases, TUNEL staining, immunohistochemistry and electromicroscope. In addition, changes of intracellular calcium were measured with confocal laser-scanning microscopy. Results F50 and F500 attenuated the decrease of TTC staining and the increase of LDH release induced by OGD in brain slices. Neuronal apoptosis and changes of neuronal uhrastructures were attenuated by F50 and F500. Bcl-2 and Bax protein expressions were increased after OGD. Bax protein expression was decreased by F50 and F500, while Bcl-2 protein expression was increased by F50 and F500. Intracellular calcium concentration was increased by OGD and then it was lowered by F50 and F500. The protective effects of F50 were more obvious than that of F500. Conclusions High concentrations of fentanyl have neuron protective effects against OGD injury in rat brain slices, and fentanyl 50μg· L^-1has more obvious protective effects than fentanyl 500μg· L^-1.

关 键 词：芬太尼 脑片 凋亡 胞内钙 缺氧缺糖损伤 

分 类 号：R-332[医药卫生] R322.81